effects and safety of infusion of low-doses of methylprednisolone in early ali and ards in children

Conditions: Acute Lung Injury; Acute Respiratory Distress Syndrome

Summary: the purpose of this study is to investigate the effects of prolonged low-dose methylprednisolone infusion on pulmonary function (lis and ventilation-free days), extra pulmonary organ function (pmods score), inflammatory markers - rcp (reactive c protein), il6 (interleukine 6), tnfα (tumor necrosis factor), il8 (interleukine 8), il10 (interleukine 10) and length of pediatric intensive care unit (picu) stay in early ali/ards in children.

scientific background. dysregulated systemic inflammation - characterized by protracted elevation of inflammatory cytokines in the circulation - is a key pathogenetic mechanism for morbidity and mortality in ali/ards, and is associated with tissue insensitivity and/or resistance to inappropriately elevated endogenous glucocorticoids. in one study, prolonged methylprednisolone treatment of ards patients resulted in rapid and sustained reduction in circulating and pulmonary levels of pro-inflammatory cytokines, chemokines, and procollagen. preliminary work. two recent metanalysis evaluating the use of low doses of corticosteroids in acute lung injury/ards in adults reported a significant physiological improvement, a sizable reduction in duration of mechanical ventilation and icu length of stay and reduction in mortality. hypothesis. we hypothesized that prolonged administration of low doses of methylprednisolone in pediatric ali/ards is safe and downregulates systemic inflammation and leads to earlier resolution of pulmonary and extra pulmonary organ dysfunction and a reduction in duration of mechanical ventilation and icu stay. objective. to investigate the effects of prolonged low-dose methylprednisolone infusion on pulmonary function (lis and ventilation-free days), extra pulmonary organ function (pmods score), inflammatory markers - rcp (reactive c protein), il6 (interleukine 6), tnfα (tumor necrosis factor), il8 (interleukine 8), il10 (interleukine 10) and length of pediatric intensive care unit (picu) stay in early ali/ards in children. study design. prospective randomized, placebo-controlled, double-blind clinical trial.

Eligibility criteria:
inclusion criteria: * diagnosis of ali/ards within the first 72 hours based on all of the following criteria: * respiratory failure requiring mechanical ventilation - via endotracheal intubation or noninvasive positive pressure ventilation; * acute onset of bilateral pulmonary densities on chest radiograph in the context of appropriate predisposing injury or illness with no evidence of left ventricular failure; * ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (pao2:fio2 ) ≤ 300 (criteria for ali) or 200 (criteria for ards) with fio2 ≥ 0,5 and peep = 5 cmh2o. * to sign the informed consent to participate. exclusion criteria: * ali/ards with more than 72 hours of diagnosis * failure to obtain written informed consent to participate in the study; * condition requiring \> 0.5mg/kg/day of prednisone equivalent (i.e., acute asthma or bronchopulmonary dysplasia) * patients enrolled in another experimental (interventional) protocol within the past 30 days, which might adversely impact on the results of this study as determined by the investigators; * primary or secondary neuromuscular dysfunction * patients using aminoglycosides combined with neuromuscular blockers * cardiopulmonary arrest within 7 days or anytime during present hospitalization prior to enrollment; * irreversible cessation of all brain function; * immunosuppression, including hiv+ status, history of bone marrow or solid organ transplantation, current malignancy, neutropenia, receiving cytotoxic therapy for any reason, and acute burn injury; * severe chronic liver disease (child-pugh class c score \> 10 points).

Keywords: ali acute lung injury ards acute respiratory distress syndrome pediatric critical care medicine inflammatory response